title: Simultaneous determination of a hydrophobic drug candidate and its metabolite in human plasma with salting-out assisted liquid/liquid extraction using a mass spectrometry friendly salt.
abstract: In previously reported applications of salting-out assisted liquid/liquid extraction (SALLE) with acetonitrile, only inorganic salts were evaluated and implemented as the salting-out reagents. A potential concern of the method for the subsequent LC-MS analysis of biological samples was that a portion of the added salt (typically of high concentration) might be extracted and affect the chromatography separation and ionization of chromatography effluents in a mass spectrometer. Here we report, for the first time, the use of a mass spectrometry friendly organic salt, ammonium acetate, as a salting-out reagent in SALLE with acetonitrile for the simultaneous quantitation of an Abbott investigational new drug ABT-869 and its hydrophilic metabolite in human plasma. The performance of SALLE with ammonium acetate was compared with that of a previously reported method with a conventional liquid/liquid extraction technique using a set of pooled incurred samples. The % differences of the measured concentrations for 24 samples from these two methods were found to be within acceptance criteria, demonstrating SALLE with ammonium acetate as a reliable sample preparation technique. The SALLE method is simple, fast (25 min/plate), easy for automation, free of drying down step, and environmentally friendly. SALLE with mass spectrometry friendly salts has been applied to regulated sample analysis of both hydrophilic and hydrophobic compounds. It is envisioned that SALLE with acetonitrile and ammonium acetate be a universal method for high throughput automated sample preparation for bioanalytical chemistry.
authors.affiliation: Department of Drug Analysis, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA.
authors.forename: Huaiqin
authors.initials: H
authors.lastname: Wu
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Katherine
authors.initials: K
authors.lastname: Norem
authors.forename: Tawakol A
authors.initials: TA
authors.lastname: El-Shourbagy
mesh_terms: D000085:Acetates / Q000097:blood* / Q000737:chemistry; D000097:Acetonitriles / Q000097:blood* / Q000737:chemistry; D002138:Calibration; D002853:Chromatography, Liquid; D015507:Drugs, Investigational; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007191:Indazoles / Q000097:blood* / Q000378:metabolism*; D013058:Mass Spectrometry / Q000379:methods*; D010671:Phenylurea Compounds / Q000097:blood* / Q000378:metabolism*; D011786:Quality Control; D012015:Reference Standards; D012680:Sensitivity and Specificity
chemical_list: D000085:Acetates; D000097:Acetonitriles; D015507:Drugs, Investigational; D007191:Indazoles; D010671:Phenylurea Compounds; C513486:linifanib; C018824:ammonium acetate; C032159:acetonitrile